ArticlePloS one2023
Testicular histone hyperacetylation in mice by valproic acid administration affects the next generation by changes in sperm DNA methylation.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Understanding the impact of valproate on male fertility: insights from preclinical and clinical meta-analysis.BMC pharmacology & toxicology · 2024Pooled it
- Paternal valproate use and impact of shared genetic susceptibility on child neurodevelopment.Scientific reports · 2025Article
- Beyond Genes: Mechanistic and Epidemiological Insights into Paternal Environmental Influence on Offspring Health.Current environmental health reports · 2025Review
- Valproic acid attenuates the severity of astrogliosis in the hippocampus of animal models of temporal lobe epilepsy.IBRO neuroscience reports · 2024Article
- New valproate regulations, informed choice and seizure risk.Journal of neurology · 2024Review
- Sperm epigenetic mechanisms in autism spectrum disorders. The valproate case illustrates an enduring and systemic failure.Molecular psychiatry · 2024Article
- A Survey of Fatty Acid Content of the Male Reproductive System in Mice Supplemented With Arachidonic Acid.Journal of lipids · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various studies have described epigenetic inheritance through sperms. However, the detailed mechanisms remain unclear. In this study, we focused on DNA methylation in mice treated with valproic acid (VPA), an inducer of epigenomic changes, and analyzed the treatment effects on the sperm from the next generation of mice. The administration of 200 mg/kg/day VPA to mice for 4 weeks caused transient histone hyperacetylation in the testes and DNA methylation changes in the sperm, including promoter CpGs of genes related to brain function. Oocytes fertilized with VPA-treated mouse sperm showed methylation fluctuations at the morula stage. Pups that were fathered by these mice also showed behavioral changes in the light/dark transition test after maturation. Brain RNA-seq of these mice showed that the expression of genes related to neural functions were altered. Comparison of the sperm DNA methylation status of the next generation of mice with that of the parental generation revealed the disappearance of methylation changes observed in the sperm of the parental generation. These findings suggest that VPA-induced histone hyperacetylation may have brain function-related effects on the next generation through changes in sperm DNA methylation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.